Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study.

BACKGROUND: Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. METHODS: A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist. RESULTS: Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration. CONCLUSION: This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.

Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons.

Remimazolam is an ultra-short benzodiazepine that acts on the benzodiazepine site of γ-aminobutyric acid (GABA) receptors in the brain and induces sedation. Although GABA receptors are found localized in the spinal dorsal horn, no previous studies have reported the analgesic effects or investigated the cellular mechanisms of remimazolam on the spinal dorsal horn. Behavioral measures, immunohistochemistry, and in vitro whole-cell patch-clamp recordings of dorsal horn neurons were used to assess synaptic transmission. Intrathecal injection of remimazolam induced behavioral analgesia in inflammatory pain-induced mechanical allodynia (six rats/dose; p < 0.05). Immunohistochemical staining revealed that remimazolam suppressed spinal phosphorylated extracellular signal-regulated kinase activation (five rats/group, p < 0.05). In vitro whole-cell patch-clamp analysis demonstrated that remimazolam increased the frequency of GABAergic miniature inhibitory post-synaptic currents, prolonged the decay time (six rats; p < 0.05), and enhanced GABA currents induced by exogenous GABA (seven rats; p < 0.01). However, remimazolam did not affect miniature excitatory post-synaptic currents or amplitude of monosynaptic excitatory post-synaptic currents evoked by Aδ- and C-fiber stimulation (seven rats; p > 0.05). This study suggests that remimazolam induces analgesia by enhancing GABAergic inhibitory transmission in the spinal dorsal horn, suggesting its potential utility as a spinal analgesic for inflammatory pain.

Omega-conotoxin MVIIA reduces neuropathic pain after spinal cord injury by inhibiting N-type voltage-dependent calcium channels on spinal dorsal horn.

Spinal cord injury (SCI) leads to the development of neuropathic pain. Although a multitude of pathological processes contribute to SCI-induced pain, excessive intracellular calcium accumulation and voltage-gated calcium-channel upregulation play critical roles in SCI-induced pain. However, the role of calcium-channel blockers in SCI-induced pain is unknown. Omega-conotoxin MVIIA (MVIIA) is a calcium-channel blocker that selectively inhibits N-type voltage-dependent calcium channels and demonstrates neuroprotective effects. Therefore, we investigated spinal analgesic actions and cellular mechanisms underlying the analgesic effects of MVIIA in SCI. We used SCI-induced pain model rats and conducted behavioral tests, immunohistochemical analyses, and electrophysiological experiments (in vitro whole-cell patch-clamp recording and in vivo extracellular recording). A behavior study suggested intrathecal MVIIA administration in the acute phase after SCI induced analgesia for mechanical allodynia. Immunohistochemical experiments and in vivo extracellular recordings suggested that MVIIA induces analgesia in SCI-induced pain by directly inhibiting neuronal activity in the superficial spinal dorsal horn. In vitro whole-cell patch-clamp recording showed that MVIIA inhibits presynaptic N-type voltage-dependent calcium channels expressed on primary afferent Aδ-and C-fiber terminals and suppresses the presynaptic glutamate release from substantia gelatinosa in the spinal dorsal horn. In conclusion, MVIIA administration in the acute phase after SCI may induce analgesia in SCI-induced pain by inhibiting N-type voltage-dependent calcium channels on Aδ-and C-fiber terminals in the spinal dorsal horn, resulting in decreased neuronal excitability enhanced by SCI-induced pain.

Induced chirality at the surface: fixation of a dynamic M/P invertible helical Co3 complex on SiO2.

Dynamic M/P invertible helicity was successfully induced at a SiO2 surface immobilized with a dynamic helical trinuclear cobalt complex, [LCo3(NHMe2)6](OTf)3, using chiral ((R) or (S))-1-phenylethylamine. Solid-state CD spectra and theoretical calculations suggested that the fixation of the M/P helical complex on the surface via coordination interactions was the key factor of the induced chirality at the surface.

Pancreatic mixed acinar-neuroendocrine carcinoma with intraductal growth: A case report with radiologic-pathologic correlations.

Pancreatic mixed acinar-neuroendocrine carcinomas are rare malignant tumors of the pancreas. They are composed histologically of both acinar and neuroendocrine cells. The pancreatic duct is known to be an important site of tumor growth for acinar cell carcinomas, neuroendocrine tumors, and intraductal tubulopapillary neoplasms. To the best of our knowledge, there has been only 1 report of a mixed acinar-neuroendocrine carcinoma growing into the pancreatic duct and no reports detailing imaging findings with this tumor. We here report a 69-year-old man who presented with worsening glycemic control. Multiphase contrast-enhanced computed tomography and magnetic resonance imaging revealed a well-circumscribed mass with poor contrast enhancement in the pancreatic tail region of the pancreatic duct. The intraductal mass showed diffusion restriction on magnetic resonance imaging. These imaging findings are consistent with the expansive, smooth-surfaced polypoid tumor of low vascularity and high cellularity that was diagnosed pathologically. Mixed acinar-neuroendocrine carcinomas should be included in the differential diagnosis of intraductal tumors of the pancreas with poor contrast enhancement and diffusion restriction.

Influence of the descending pain-inhibiting serotonergic pathway on the antihyperalgesic effect of gabapentin in neuropathic pain model rats.

Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia.

Mathematical models of the solid cancer induced by atomic bomb and the spontaneous cancer in the daily life-Proposal of a new medical treatment for cancers.

BACKGROUND: A mathematical model of the radiation-induced cancer was devised to explain the change of incidence rates pursued by Radiation Effect Research Foundation for 25 years. AIM: The aim of this work is construction of mechanisms of radiation-induced cancer and cancers observed in the daily life. METHODS AND RESULTS: First, we found a way to separate spontaneous cancers from radiation-induced cancers observed among atomic-bomb victims in Hiroshima and Nagasaki districts by using a constructed algorithm. The isolated incidence rates of radiation-induced cancers were reproduced by a two-stage model mechanical collision of impinging radiation with cells and succeeding mutation of the damaged cell to cancer. This model satisfactorily reproduced observed solid cancer incidence rates. We further attempted to construct a mathematical model for the age-dependence of spontaneous cancers appearing in the daily life and concluded that the cancer should be generated at cell division. CONCLUSION: With these findings, we reached to a conclusion that cancers may be suppressed by eliminating damaged cells with mild-dose radiation.

Structural and functional properties of spinal dorsal horn neurons after peripheral nerve injury change overtime via astrocyte activation.

Chronic pain remains challenging to treat, despite numerous reports of its pathogenesis, including neuronal plasticity in the spinal dorsal horn (SDH). We hypothesized that understanding plasticity only at a specific time point after peripheral nerve injury (PNI) is insufficient to solve chronic pain. Here, we analyzed the temporal changes in synaptic transmission and astrocyte-neuron interactions in SDH after PNI. We found that synaptic transmission in the SDH after PNI changed in a time-dependent manner, which was accompanied by astrocyte proliferation and loss of inhibitory and excitatory neurons. Furthermore, neuronal loss was accompanied by necroptosis. Short-term inhibition of astrocytes after PNI suppressed these physiological and morphological changes and long-term pain-related behaviors. These results are the first to demonstrate that the inhibition of astrocyte proliferation after PNI contributes to the long-term regulation of plasticity and of necroptosis development in the SDH.

Spinal intraosseous arteriovenous fistulas with perimedullary drainage associated with vertebral compression fracture: illustrative case.

BACKGROUND: Although osseous involvement is occasionally observed in spinal epidural arteriovenous fistulas (AVFs) or seen as a part of diseases of spinal arteriovenous metameric syndrome, purely intraosseous spinal AVFs are extremely rare. Their clinical and imaging characteristic features are not well known. The authors present a case of purely intraosseous AVFs associated with compression fracture. OBSERVATIONS: A 76-year-old man presented with back pain and progressive myelopathy. Computed tomography showed compression fracture of the T12 vertebral body and dilatation of perimedullary veins. Spinal angiography revealed an intraosseous AVF at the T12 spine level, which was fed by multiple feeders of ventral somatic branches and drained into the paravertebral and perimedullary veins. The intraosseous AVF was completely occluded by the combined techniques of transarterial and transvenous embolization with glue and a coil. The symptoms disappeared within 1 month after embolization. LESSONS: Although extremely rare, spinal intraosseous AVFs can develop after compression fracture and cause congestive myelopathy. Combined transarterial and transvenous embolization is useful for the specific case of spinal intraosseous AVFs with both paravertebral and perimedullary drainage.

Epidural administration of 2% Mepivacaine after spinal anesthesia does not prevent intraoperative nausea and vomiting during cesarean section: A prospective, double-blinded, randomized controlled trial.

BACKGROUND: Intraoperative nausea and vomiting (IONV) is a common symptom during cesarean section (CS) delivery causing significant discomfort to patients. Combined spinal and epidural anesthesia (CSEA) can provide both intraoperative anesthesia and postoperative analgesia. During CSEA, it is reasonable to administer local anesthetics to the epidural space before patient complaints to compensate for the diminished effect of spinal anesthesia. Therefore, we hypothesized that intraoperative epidural administration of 2% mepivacaine would reduce the incidence of IONV. METHODS: Patients who were scheduled for elective CS were randomly allocated to 2 groups. Patients and all clinical staff except for an attending anesthesiologist were blinded to the allocation. After the epidural catheter was inserted at the T11-12 or T12-L1 interspace, spinal anesthesia was performed at the L2-3 or L3-4 interspace to intrathecally administer 10 mg of 0.5% hyperbaric bupivacaine. Twenty min after spinal anesthesia, either 5 mL of 2% mepivacaine (group M) or saline (group S) was administered through an epidural catheter. Vasopressors were administered prophylactically to keep both the systolic blood pressure ≥ 80 % of the baseline value with the absolute value ≥ 90 mm Hg and the mean blood pressure ≥ 60 mm Hg. The primary endpoint was the incidence of IONV. The secondary endpoints were degree of nausea, the degree and incidence of pain, and Bromage score. RESULTS: Ninety patients were randomized, and 3 patients were excluded from the final analysis. There was no significant difference in the incidence of IONV between the groups (58% in group M and 61% in group S, respectively, P = .82). In contrast, the incidence and degree of intraoperative pain in group M were significantly lower compared to group S. In addition, the incidence of rescue epidural administration of fentanyl (18% vs 47%) or mepivacaine (2.3% vs 25%) for intraoperative pain was lower in group M compared to group S. CONCLUSIONS: Our results indicate that epidural administration of 2% mepivacaine 20 minutes after spinal anesthesia does not reduce the incidence of IONV in CS under CSEA. However, intraoperative epidural administration of 2% mepivacaine was found to improve intraoperative pain.

Asymmetric epileptic spasms after corpus callosotomy in children with West syndrome may be a good indicator for unilateral epileptic focus and subsequent resective surgery.

OBJECTIVE: This retrospective study was designed to observe differences in ictal movements of epileptic spasm (ES) before and after corpus callosotomy (CC). We hypothesized that asymmetric expression of ES is more clarified after CC and would be a good indicator for the epileptic hemisphere. METHODS: We selected 16 patients with intractable ES in West syndrome who were seizure-free after CC and subsequent resection or disconnective surgery of the unilateral hemisphere. We retrospectively reviewed their behavioral ES recorded at video-electroencephalography monitoring before and after CC. Asymmetric neck flexion (NF) and involuntary muscular contraction of the upper and lower extremities (MCU and MCL, respectively) were primarily described correlating their laterality and the responsible hemisphere proved by surgical resection. RESULTS: Asymmetric NF, MCU, and MCL could be found both before and after CC. However, the percentage of those movements to the total number of ES increased after CC; asymmetric NF, 82.9% vs. 20.1%; unilaterally predominant MCU, 81% vs. 39.3%; and unilaterally predominant MCL, 77.6% vs. 29.9%. Regarding asymmetric NF, the direction in which the neck flexed or the head turned was significantly ipsilateral to the responsible hemisphere in 9 of 12 patients after CC (75%). The predominant side of MCU and MCL were significantly contralateral to the responsible hemisphere in 11 of 11 and 7 of 9 patients (100% and 77.8%, respectively). SIGNIFICANCE: Asymmetric NF, MCU, and MCL were clarified in patients with ES who were successfully treated with CC and subsequent surgery. Those changes in ictal behaviors after CC may indicate the lateralization of epileptic activity and encourage more curative surgical treatment.

Analgesic effect of ivabradine against inflammatory pain mediated by hyperpolarization-activated cyclic nucleotide-gated cation channels expressed on primary afferent terminals in the spinal dorsal horn.

ABSTRACT: Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel blocker and clinically approved bradycardic agent, has analgesic effects against neuropathic pain. Although the expression of HCN channels in the spinal dorsal horn (SDH) is augmented under inflammatory pain, spinal responses to centrally and peripherally applied ivabradine remain poorly understood. We investigated the spinal action and cellular mechanisms underlying the drug's analgesic effects against inflammatory pain using inflammatory pain model rats. Intraperitoneal and intrathecal injections of ivabradine inhibited mechanical allodynia (6 rats/dose; P < 0.05), and immunohistochemical staining showed that ivabradine suppresses the phosphorylated extracellular signal-regulated kinase activation in the SDH (6 rats/group, P < 0.01). In vitro whole-cell patch-clamp and in vivo extracellular recordings showed that direct application of ivabradine to the spinal cord decreases the mean miniature excitatory postsynaptic currents' frequency (13 rats; P < 0.01), and direct and peripheral application of ivabradine suppresses the spinal response to mechanical stimulation-evoked firing (8 rats/group, P < 0.01). Moreover, ivabradine reduces the amplitudes of monosynaptic excitatory postsynaptic currents evoked by Aδ-fiber and C-fiber stimulation (6 rats; P < 0.01) and induces a stronger inhibition of those evoked by C-fiber stimulation. These phenomena were inhibited by forskolin, an activator of HCN channels. In conclusion, spinal responses mediated by HCN channels on primary afferent terminals are suppressed by central and peripheral administration of ivabradine; the drug also exhibits analgesic effects against inflammatory pain. In addition, ivabradine preferentially acts on C-fiber terminals of SDH neurons and induces a stronger inhibition of neuronal excitability in inflammatory pain.

Neuronal Nitric Oxide Synthase Suppression Confers the Prolonged Analgesic Effect of Sciatic Nerve Block With Perineural Dexamethasone in Postoperative Pain Model Mice.

Dexamethasone supplementation to local anesthetics prolongs its action, yet the underlying mechanism is unclear. Previous studies have reported that increased p-p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglia (DRG) is associated with pain-associated behavior and that nitric oxide (NO), which is known to be a pronociceptive substance, directly inhibits sciatic nerve conduction. Here, we investigated the temporal changes in the hyperalgesic effect and p-p38 MAPK and NO synthase (NOS) expression levels in the DRG when dexamethasone was added to ropivacaine used for a sciatic nerve block (SNB) in postoperative pain model mice. Dexamethasone supplementation to ropivacaine significantly prolonged the analgesic effect of SNB via glucocorticoid receptor activation. Histological examination revealed that ropivacaine suppressed p-p38 MAPK expression in the DRG regardless of dexamethasone supplementation, suggesting that p-p38 MAPK was not involved in the prolonging effect of dexamethasone on nerve block. Contrastingly, plantar incision markedly increased the expression of neuronal NOS (nNOS) in DRG, and dexamethasone supplementation to ropivacaine significantly suppressed nNOS expression. Supplementation of L-NAME, an inhibitor of NOS, to ropivacaine markedly prolonged the effect of SNB, similar to dexamethasone. These results suggest that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting nNOS activity. PERSPECTIVE: The current study revealed that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting the activity of neuronal NOS and that p-p38 MAPK may not be involved in this phenomenon. Our findings offer a new target for the discovery of long-acting local anesthetics.

Norepinephrine Restores Inhibitory Tone of Spinal Lamina X Circuitry, thus Contributing to Analgesia Against Inflammatory Pain.

Norepinephrine (NE) acts directly on the inhibitory interneurons of spinal lamina X and may act on spinal lamina X neurons for inhibiting nociceptive synaptic transmission against pain. We investigated this mechanism within inflammatory pain model rats. Using immunohistochemical staining and in vivo extracellular recording, the increased number of phosphorylated extracellular signal-regulated kinase profiles in lamina X (n = 6/group) and increased frequency of spontaneous neuronal firing on putative lamina X (n = 14) under the inflammatory pain were significantly suppressed by the direct application of NE (P < 0.01). Following in vivo observation of enhanced spontaneous neuronal firing, we tested the impact of NE on this discharge using an in vitro spinal slice preparation. Using in vitro patch-clamps recording, the baseline level of miniature inhibitory postsynaptic currents (mIPSCs) frequency on spinal lamina X neurons cord is decreased under inflammatory pain. Direct application of NE to spinal lamina X neurons in inflammatory pain model rats facilitates mIPSCs frequency and induces an outward current (n = 8; P < 0.05), and these responses are inhibited by α1A- and α2-receptor antagonists (n = 8; P > 0.05). Considering these results and those of our previous study (Ohashi et al., 2019), NE might act on inhibitory interneurons of spinal lamina X to facilitate inhibitory transmission and induces neurons located in or around lamina X membrane hyperpolarization. These NE-mediated responses acted through α1A- and α2-receptors. These mechanisms of NE on spinal lamina X might contribute to analgesia against inflammatory pain.

Low-dose Droperidol Reduces the Amplitude of Transcranial Electrical Motor-evoked Potential: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes. METHODS: Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range). RESULTS: The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P <0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group. CONCLUSIONS: Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.

Effects of the Kampo medicine Yokukansan for perioperative anxiety and postoperative pain in women undergoing breast surgery: A randomized, controlled trial.

Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In this randomized controlled trial, we compared the subjective assessment of anxiety using questionnaires and its objective assessment using salivary alpha-amylase concentrations in YKS and control (CNT) groups of women undergoing breast surgery. The trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000028998), and the investigators were blinded to drug administration. One hundred patients who underwent breast cancer surgery were allocated to either the YKS or the CNT group. Finally, 35 and 42 patients in the YKS and CNT groups were analyzed, respectively. The YKS group received two 2.5 g doses of the medication before sleeping on the night before surgery and 2 h before inducing anesthesia, while the CNT group did not receive medication preoperatively. Patients answered two questionnaires, the Hospital Anxiety and Depression Scale and the State-Trait Anxiety Inventory, pre-and postoperatively as subjective anxiety assessments. As an objective anxiety indicator, salivary alpha-amylase levels were measured the day before, directly before, and the day after surgery (T3). In the YKS group, salivary alpha-amylase scores directly before operation were significantly lower than those on the day before surgery and at one day postoperatively (F [2,150] = 3.76, p = 0.03). Moreover, the Hospital Anxiety and Depression Scale-Anxiety and State-Trait Anxiety Inventory-Trait scores were significantly more improved postoperatively in the YKS group than in the CNT group (difference in Hospital Anxiety and Depression Scale-Anxiety: YKS, mean -2.77, 95% confidence interval [-1.48 --4.06], p <0.001, and CNT, -1.43 [-0.25--2.61], p = 0.011; and difference in State-Trait Anxiety Inventory: YKS group, -4.23 [-6.95--1.51], p = 0.0004; and CNT group, 0.12 [-2.36-2.60], p = 0.92). No side effects were associated with YKS. YKS may reduce perioperative anxiety in patients undergoing surface surgery.

Propofol reduces the amplitude of transcranial electrical motor-evoked potential without affecting spinal motor neurons: a prospective, single-arm, interventional study.

PURPOSE: Propofol inhibits the amplitudes of transcranial electrical motor-evoked potentials (TCE-MEP) in a dose-dependent manner. However, the mechanisms of this effect remain unknown. Hence, we investigated the spinal mechanisms of the inhibitory effect of propofol on TCE-MEP amplitudes by evaluating evoked electromyograms (H-reflex and F-wave) under general anesthesia. METHODS: We conducted a prospective, single-arm, interventional study including 15 patients scheduled for spine surgery under general anesthesia. Evoked electromyograms of the soleus muscle and TCE-MEPs were measured at three propofol concentrations using target-controlled infusion (TCI: 2.0, 3.0, and 4.0 µg/mL). The primary outcome measure was the left H-reflex amplitude during TCI of 4.0- compared to 2.0-µg/mL propofol administration. RESULTS: The median [interquartile range] amplitudes of the left H-reflex were 4.71 [3.42-6.60] and 5.6 [4.17-7.46] in the 4.0- and 2.0-µg/mL TCI groups (p = 0.4, Friedman test), respectively. There were no significant differences in the amplitudes of the right H-reflex and the bilateral F-wave among these groups. However, the TCE-MEP amplitudes significantly decreased with increased propofol concentrations (p < 0.001, Friedman test). CONCLUSION: Propofol did not affect the amplitudes of the H-reflex and the F-wave, whereas TCE-MEP amplitudes were reduced at higher propofol concentrations. These results suggested that propofol can suppress the TCE-MEP amplitude by inhibiting the supraspinal motor pathways more strongly than the excitability of the motor neurons in the spinal cord.

Developmental outcome after corpus callosotomy for infants and young children with drug-resistant epilepsy.

AIM: To examine the developmental and seizure outcomes after corpus callosotomy (CC) in early childhood. METHODS: We retrospectively identified 106 patients who underwent CC for drug-resistant epilepsy before the age of 6 years, at the Nagasaki Medical Center, between July 2002 and July 2016. Patients' developmental outcomes were evaluated one year after CC using the Kinder Infant Development Scale. RESULTS: The mean preoperative developmental quotient (DQ) was 25.0 (standard deviation [SD], 20.8), and the mean difference between preoperative DQ and one-year postoperative DQ was -1.6 points (SD, 11.6). However, 42.5% of patients had a mean DQ increase of 6.5 points (SD, 6.4), one year after CC from that before surgery. Factors related to the improvement in postoperative DQ were 'low preoperative DQ', 'developmental gain 1 month postoperatively', and 'postoperative seizure-free state'. Approximately 21.7% of patients were seizure-free 1 year after CC. INTERPRETATION: Performing CC, in infancy and early childhood for patients with drug-resistant epilepsy and severe developmental impairment, was associated with improved development in 42.5% of patients. Remission of seizures, even if only for a short period, contributed to developmental improvement. From a developmental perspective, CC for drug-resistant epilepsy in early childhood is an effective treatment.

A Bolus Dose of Ketamine Reduces the Amplitude of the Transcranial Electrical Motor-evoked Potential: A Randomized, Double-blinded, Placebo-controlled Study.

BACKGROUND: A low-dose bolus or infusion of ketamine does not affect transcranial electrical motor-evoked potential (MEP) amplitude, but a dose ≥1 mg/kg may reduce MEP amplitude. We conducted a randomized, double-blinded, placebo-controlled study to evaluate the effect of ketamine (1 mg/kg) on transcranial electrical MEP. METHODS: Twenty female patients (aged 12 to 18 y) with adolescent idiopathic scoliosis scheduled to undergo posterior spinal fusion were randomly allocated to receive ketamine or saline. General anesthesia was induced and maintained with continuous infusions of propofol and remifentanil. MEP was elicited by supramaximal transcranial electrical stimulation. MEP recordings were obtained at baseline and then at 2, 4, 6, 8, and 10 minutes after administration of ketamine (1 mg/kg) or saline (0.1 ml/kg). The primary endpoint was the minimum relative MEP amplitude (peak-to-peak amplitude, % of baseline value) recorded from the left tibialis anterior muscle. The baseline amplitude recorded before test drug administration was defined as 100%. RESULTS: Medians (interquartile range) minimum MEP amplitudes in the left tibialis anterior muscle in the ketamine and saline groups were 26% (9% to 34%) and 87% (55% to 103%) of the baseline value, respectively (P<0.001). MEP amplitudes in other muscles were significantly reduced by ketamine. The suppressive effect of ketamine lasted for at least 10 minutes in each muscle. CONCLUSION: A 1-mg/kg bolus dose of ketamine can reduce MEP amplitude. Anesthesiologists should consider the dosage and timing of intravenous ketamine administration during MEP monitoring.